High levels of intracellular ATP prevent nitric oxide-induced apoptosis in rat gastric mucosal cells

Kenichi Honda, Katsuaki Kato, Naohiro Dairaku, Katsunori Iijima, Tomoyuki Koike, Akira Imatani, Hitoshi Sekine, Shuichi Ohara, Hiroshi Matsui, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

Summary. Nitric oxide (NO) plays an important role in gastric mucosal injury in the human stomach. Exposure to excessive NO leads to apoptosis; however, the mechanism remains largely unknown in gastric epithelial cells. The apoptotic process is modulated by energy states in cells. This study investigated molecular mechanisms of NO-induced apoptosis in gastric epithelial cells and influence of high glucose on those mechanisms. Normal rat gastric mucosal epithelial (RGM-1) cells were cultured in media containing either 1000 (low) or 4500 mg/l (high) of D-glucose. When the cells were incubated with a chemical NO donor NOC18, apoptosis was induced in a dose-dependent manner. Intracellular adenosine triphosphate (ATP) levels significantly increased in the cells cultured with high glucose in comparison with the low-glucose condition. The cells with high ATP levels were more resistant to NO-induced apoptosis than the cells with low ATP levels. NO-induced apoptosis was followed by mitochondrial depolarization, upregulation of Bax protein, cytochrome C release from mitochondria to the cytosol and subsequent caspases activation. These results suggest that NO inhibition of mitochondrial respiratory system and acute ATP depletion initiate apoptotic signalling in gastric epithelial cells. High glucose may prevent NO-induced apoptosis by leading to high levels of intracellular ATP or other metabolic changes in this cell line.

Original languageEnglish
Pages (from-to)281-288
Number of pages8
JournalInternational Journal of Experimental Pathology
Volume84
Issue number6
DOIs
Publication statusPublished - 2003 Dec

Keywords

  • ATP
  • Apoptosis
  • Glucose
  • Mitochondria
  • Nitric oxide
  • Stomach

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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